Levinthal's paradox

With Levinthal paradox Cyrus Levinthal described the problem of molecular biology, such as an amino acid chain its functional folded state is used as a protein in a short time.

Description of the problem

The underlying combinatorial problem is that the number of possible folds of a protein having the amino acid chain length increases exponentially. Even if each amino acid residue could assume only two states, there would be at a protein length of n amino acids possible folding variants. Would a change in the conformation need about seconds, so would need a 150 amino acid protein that is over -year, to find the optimum conformation (see time complexity). In fact, proteins often have a half-life of a few hours to days, and the physiologically folded ( native) form is usually taken quickly ( fractions of seconds to minutes). Thus, the convolution can not be explained by a random testing every possibility. Rather, there are natural mechanisms which favor the formation of the optimal folding.

Importance in bioinformatics

The problem with this " combinatorial explosion " also arises in the simulation or calculation of the protein structure in silico, ie in Bioinformatics: What is known about the mechanisms of protein folding, it is not yet used for the simulation of the folding itself. Therefore, in a simulation of substantially all possible conformations need to be calculated. The one with the lowest energy state is selected.

Importance for the formation of protein

The Levinthal paradox is basically not a scientific problem, but was formulated to illustrate the complexity of protein folding educational.

The Levinthal paradox is subject to the assumption that the complete amino acid chain seeking their physiological three-dimensional shape only after it was fully synthesized under trying out a myriad of possible conformations. In fact, each link takes upon entry into the sequence a, the energetically most favorable direction in space, for which the time is sufficient to append the next. Neighbouring sequence segments fold spontaneously into smaller stable structural domains.

Supporting mechanisms may accompany the folding process, including folding helper proteins, molecular chaperones and " convolution kernels " (stable, smaller associations of structural elements that fold quickly and draw the rest of the structure in an energy minimum, that is the correct structure collapses " "on the convolution kernel ). But also non-physiological "helper" may be involved, such as prions.